2-喹啉羧酸,3-(苯基甲氧基)-,甲基酯 | 171917-54-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 中文名称: 2-喹啉羧酸,3-(苯基甲氧基)-,甲基酯
• 英文名称: Methyl 3-(benzyloxy)quinoline-2-carboxylate
• 英文别名: Methyl 3-(benzyloxy)-2-quinolinecarboxylate；methyl 3-phenylmethoxyquinoline-2-carboxylate
• CAS: 171917-54-7
• 化学式: C₁₈H₁₅NO₃
• 分子量: 293.322
• InChiKey: ZAKXHCSIHRWMJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  48.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-喹啉羧酸,3-(苯基甲氧基)-,甲基酯 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 25.0 ℃ 、101.32 kPa 条件下， 反应 5.0h， 以96%的产率得到3-羟基喹啉-2-羧酸
  参考文献：
  名称：

  A Modified Friedlander Condensation for the Synthesis of 3-Hydroxyquinoline-2-carboxylates

  摘要：

  DOI：

  10.1021/jo00127a055
• 作为产物：
  描述：

  2-氨基苯甲醛 在 四丁基碘化铵 氢氧化钾 、 碳酸氢钠 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 72.0h， 生成 2-喹啉羧酸,3-(苯基甲氧基)-,甲基酯
  参考文献：
  名称：

  A Modified Friedlander Condensation for the Synthesis of 3-Hydroxyquinoline-2-carboxylates

  摘要：

  DOI：

  10.1021/jo00127a055

文献信息

• Structure–Activity Relationships of Bis-Intercalating Peptides and Their Application as Antibody–Drug Conjugate Payloads
  作者：Mark E. Petersen、Michael G. Brant、Manuel Lasalle、Vincent K. C. Fung、Andrea Hernandez Rojas、Jodi Wong、Samir Das、Stuart D. Barnscher、Jamie R. Rich、Geoffrey C. Winters

  DOI：10.1021/acs.jmedchem.3c00760

  日期：2023.6.22

  payloads. Synthesis, biophysical characterization, and in vitro potency of 34 new analogs are described. Conjugation of an initial drug-linker derived from a novel bis-intercalating peptide produced an ADC that was hydrophobic and prone to aggregation. Two strategies were employed to improve ADC physiochemical properties: addition of a solubilizing group in the linker and the use of an enzymatically cleavable

  研究了基于 DNA 双嵌入天然产物肽沙霉素和喹哪肽的合成类似物作为抗体药物偶联物 (ADC) 的有效负载。描述了 34 种新类似物的合成、生物物理表征和体外效力。源自新型双嵌入肽的初始药物接头的缀合产生了疏水性且易于聚集的 ADC。采用两种策略来改善 ADC 的理化特性：在接头中添加增溶基团以及在有效负载本身上使用酶促裂解的亲水掩模。所有 ADC 均在体外表现出有效功效高抗原表达细胞的细胞毒性；然而，在抗原表达较低的细胞系中，掩蔽的 ADC 不如有效负载匹配的未掩蔽的 ADC 有效。使用随机缀合的 DAR4 抗 FRα ADC 和位点特异性缀合 (THIOMAB) DAR2 抗 cMet ADC 进行了两项试点体内研究，前者即使在低剂量下也显示出毒性，后者耐受性良好且非常有效。
• Synthesis of key sandramycin analogs: systematic examination of the intercalation chromophore
  作者：Dale L. Boger、Jyun-Hung Chen、Kurt W. Saionz、Qing Jin

  DOI：10.1016/s0968-0896(97)10014-1

  日期：1998.1

  The preparation and examination of 2-22 constituting a systematic study of the chromophore of sandramycin (1) are detailed. Fluorescence quenching studies were used to establish binding constants for 1-24 within calf thymus DNA, within a single high affinity bis-intercalation binding site 5'-d(GCATGC)(2), and to establish the preference for sandramycin binding to 5'-d(GCXXGC)(2) where XX = AT, TA, GC, and CG. From the latter studies, sandramycin was found to exhibit a preference that follows the order: 5'-d(GCATGC)(2) > 5'-d(GCGCGC)(2), Delta Delta G degrees = 0.3 kcal/mol > 5'-d(GCTAGC)(2), 5'-d(GCCGGC)(2), Delta Delta G degrees = 0.6 kcal/mol although it binds with high affinity to all four deoxyoligonucleotides. The two highest affinity sequences constitute repeating 5'-PuPy motifs with each intercalation event occurring at a 5'-PyPu step. The most effective sequence constitutes the less stable duplex, contains the sterically most accessible minor groove central to the bis-intercalation site, and the ability to accept two gly-NH/T C2 carbonyl H-bonds identified in prior NMR studies. Similarly, the contribution of the individual structural features of the chromophore were assessed with the high affinity duplex sequence 5'-d(GCATGC)(2). To a first approximation, the cytotoxic properties were found to parallel trends established in the DNA binding affinities. The exception to this generalization was 4 which lacks the sandramycin chromophore phenol. Although typically 4-10x less potent than sandramycin against leukemia cell lines, it proved to be 1-10,000x more potent against melanomas, carcinomas, and adenocarcinomas exhibiting IC50 values of IpM-10 nM placing it among the most potent agents identified to date. Additionally, the first disclosure of the HIV-1 reverse transcriptase inhibitory activity of sandramycin (1) as well as that of its key analogs are described and define the chromophore structural features required for their exceptional potency. Two analogs, 18 and 3, roughly maintain the HIV-I reverse transcriptase inhibitory potency of 1 but exhibit substantially diminished cytotoxic activity (10(2) - 10(3)x). (C) 1998 Elsevier Science Ltd. All rights reserved.